Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes

Valeria Judkowski, Enrique Rodriguez, Clemencia Pinilla, Emma Masteller, Jeffrey A. Bluestone, Nora Sarvetnick, Darcy B. Wilson

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

NOD mice spontaneously develop insulitis and type 1 diabetes (T1D) mellitus similar to humans. Insulitis without overt disease occurs in the BDC2.5 TCR-transgenic NOD mice that express the rearranged TCR α- and β-chain genes of a diabetogenic T cell clone reactive to an unknown β cell autoantigen. A previous study identified an extensive panel of peptides that are highly active in stimulating T cells from transgenic BDC2.5 mice in culture. However, none of these peptides cause active disease in NOD and BDC2.5 animals or in NOD recipients of adoptively transferred BDC2.5 T cells following direct immunization in vivo. We show that direct immunization of transgenic BDC2.5 mice causes many BDC2.5 T cells to become activated and apoptotic. Strikingly, soluble peptides administered to recipients of activated, highly pathogenic BDC2.5 T cells results in protection from disease. These results suggest that high affinity peptide analogues of autoimmune epitopes might be useful as therapeutic modulators in active autoimmune disease.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalClinical Immunology
Volume113
Issue number1
DOIs
StatePublished - Oct 2004

Keywords

  • Autoimmunity
  • BDC2.5 mice
  • Diabetes
  • EC
  • IDDM
  • NOD
  • NOD mice
  • Peptide antigens
  • SI
  • T cell receptor
  • T1D
  • TCR
  • insulin-dependent diabetes mellitus
  • nonobese diabetic
  • the concentration of peptide that stimulates a half-maximal response
  • type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Judkowski, V., Rodriguez, E., Pinilla, C., Masteller, E., Bluestone, J. A., Sarvetnick, N., & Wilson, D. B. (2004). Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes. Clinical Immunology, 113(1), 29-37. https://doi.org/10.1016/j.clim.2004.03.007